Laboratory tests to identify suitable gene vectors for targeted tumor gene therapy in colorectal and kidney cancer

Colon and renal cell carcinomas are malignant tumors of the colon and the kidney, respectively, which are usually removed surgically. Especially for tumors above a certain size, a more extensive surgical procedure such as a hemicolectomy (removal of a section of the large intestine) or a nephrectomy (removal of a kidney) is often performed. Since tumor tissue is removed during these procedures anyway, it is particularly well-suited for experimental research without affecting the actual treatment of the patients.

Gene therapy is a relatively new approach in cancer treatment that aims to deliver therapeutic genes directly into cancer cells to inhibit tumor growth or specifically destroy the tumor cells. So-called gene carriers (vectors) are used for this purpose; they serve as transport vehicles and deliver the genetic information to the target cell. AAV vectors (adeno-associated viruses) are used particularly frequently in this context. These are harmless viruses that do not cause disease in humans. They are generally well tolerated and trigger only minimal immune responses. There are many different AAV vectors whose envelope proteins can be specifically modified to improve their ability to recognize and bind to tumor cells in the laboratory. Since tumor cells differ from one another depending on tissue type and origin (including surface characteristics and blood supply), it is necessary to identify suitable AAV vectors for each type of tumor. A vector suitable for liver metastases may be much less effective against tumors of the lung or kidneys.

AAV vectors are already approved for use in treating some rare genetic disorders (e.g., spinal muscular atrophy), but are not yet routinely used in cancer treatment. The goal of the AAV-AH-OI-01 study is to identify, from a wide range of AAV vectors, those variants that are particularly effective at penetrating tumor cells in colorectal or renal cell carcinomas. The goal is not merely to find a vector for a single tumor, but to identify vectors that work as reliably as possible for these types of cancer, so that many patients can benefit in the long term. The long-term goal is to develop vectors that reliably reach the tumor tissue and can be used systemically (distributed throughout the body via the bloodstream) in future treatments. To this end, the patients’ tumor tissue—which is removed anyway—is used for laboratory analysis. In the laboratory, the removed tumor tissue is perfused with a fluid containing various AAV vectors (“ex vivo perfusion”). The study then determines which AAV vectors are most effective at penetrating the tumor cells. The study is intended for basic research and does not affect the actual treatment of the participating patients.

Eligible participants are women and men aged 18 and older with untreated colon or renal cell carcinoma with a tumor size of at least 2 cm, who are scheduled to undergo a hemicolectomy or nephrectomy.